Placental Hypoxia Developed During Preeclampsia Induces Telocytes Apoptosis in Chorionic Villi Affecting The Maternal-Fetus Metabolic Exchange.

Telocytes (TC) are a new type of stromal cells initially found and studied in digestive and extra- digestive organs. These cells have a small cell body with 2 to 5 thin and extremely long cytoplasmic prolongations named telopodes. In recent years, TC have also been described in placental chorionic villi, located in a strategical position between the smooth muscle cells from fetal vessels and the myofibroblasts in the stromal villi. Unlike other organs, the placenta is not innervated and considering the strategic location of TC is has been postulated that TC function would be related to signal transduction mechanisms involved in the regulation of the fetal vessels blood flow, as well as in the shortening/lengthening of the chorionic villi, providing the necessary rhythmicity to the process of maternal/fetal metabolic exchange. Preeclampsia (PE) is a systemic syndrome that affects 4%-6% of pregnancies worldwide. It is characterized by a placental state of ischemia-hypoxia which triggers an oxidative stress stage with the concomitant production of reactive oxygen species (ROS) leading to an increase in the degree of placental apoptosis. Placental vascular tone is regulated by the vasodilator nitric oxide (NO) and, in PE cases, NO is diverted towards the formation of peroxynitrite, a powerful oxidative agent whose activity leads to an increase of placental apoptosis degree that compromises TC and myofibroblasts, a key feature we would like to emphasize in this work.

Oxidative damage to pre-eclamptic placenta: immunohistochemical expression of VEGF, nitrotyrosine residues and von Willebrand factor.

OBJECTIVE: To determine the relationship of biomarkers of placental damage by oxidative stress in pre-eclamptic placenta. METHODS: A case-control study was performed on a population of 14 pregnant women with PE and 12 women with normal pregnancies. Immunohistochemical expressions of VEGF, vWF distribution, (Na + K)-ATPase activity, and abundance of nitrotyrosine residues, were assessed in the placental tissue. RESULTS: Women with pre-eclampsia showed increased VEGF expression and abundance of nitrotyrosine residues in placental villous, and plasma vWF levels (p < 0.05), whereas placental (Na + K)-ATPase activity were significantly reduced. The syncytiotrophoblast and the maternal space of pre-eclamptic placenta showed diminished and increased vWF expression, respectively, but no significant differences in its expression were found in the placental endothelium and stroma (p < 0.05). CONCLUSIONS: It could be suggested that increased oxidative stress and VEGF contribute to enhance the impairment of placental perfusion by increasing peroxynitrite formation, product of the NO and superoxide reaction, thereby partly contributing to account for the pathophysiology of this disease. The presence of vWF in the maternal space and its diminished expression in syncytiotrophoblast of pre-eclamptic placenta also might have pathogenic implications.

First-trimester adiponectin and subsequent development of preeclampsia or fetal growth restriction.

BACKGROUND/AIMS: The evidence regarding the utility of assessing first-trimester adiponectin (ApN) serum levels in early prediction of preeclampsia (PE) and fetal growth restriction (FGR) is contradictory. This study aims to determine the role of maternal serum ApN levels as an early predictor of PE and FGR. METHODS: A prospective case-control study among a pregnant population who attended their 11- to 14-week ultrasound scan at the University of Chile's Clinical Hospital's Fetal Medicine Unit. We included patients who developed PE or FGR (10 cases per group) and 35 healthy controls. We determined ApN levels in blood samples from these 55 patients using a commercial ELISA kit and assessed the relationship of ApN levels with variables like development of PE, FGR, weight at birth and maternal BMI. RESULTS: There were no significant differences among first-trimester ApN serum levels in the groups. Average concentrations were 8, 6.8 and 10.8 ng/ml for the control, PE and FGR groups, respectively. CONCLUSION: In our study, maternal serum ApN levels were not useful in predicting subsequent development of PE and FGR. However, maternal serum ApN concentration adjusted by BMI was significantly higher during the first trimester in women who later developed FGR.

Immunohistochemical expression of von Willebrand factor in the preeclamptic placenta.

Preeclampsia is a high-prevalence systemic pregnancy disorder associated with maternal and foetal mortality. Its pathogenesis is unknown, but it is thought that oxidative stress and endothelial dysfunction may play a fundamental role. Von Willebrand factor (vWF), a marker of endothelial cell injury, can be found in different cells and zones of the placenta. To determine the differential immunoexpression of vWF at different tissue types of preeclamptic placenta and endothelial dysfunction markers at maternal serum of preeclamptic pregnancies. A case-control study was performed on a population of pregnant women with preeclampsia (n = 14), and normal pregnancies (n = 8). Placental and blood plasma samples were withdrawn at delivery. Immunohistochemical vWF expression in the placental tissue was determined. Endothelial dysfunction was assessed through plasminogen activator inhibitor (PAI) 1 and 2 ratio and vWF concentration in maternal plasma. P values less than 0.05 were considered statistically significant. Preeclamptic women showed increased plasma PAI-1/PAI-2 ratio (P < 0.05). There was diminished placental vWF expression in syncytiotrophoblast and increased in the intervillous space of preeclamptic placentas (P < 0.05). No significant differences in vWF expression were found in the villous endothelium and stroma, but it was significantly higher in maternal plasma (P < 0.05). In preeclampsia occurs endothelial damage and placental cell injury. Cell damage in syncytiotrophoblast that occurs in preeclampsia could liberate vWF from syncytiotrophoblast to the placental intervillous space, and this may have pathogenic implications.

Screening test for preeclampsia through assessment of uteroplacental blood flow and biochemical markers of oxidative stress and endothelial dysfunction.

OBJECTIVE: This study was undertaken to evaluate whether screening through a uterine artery (UtA) Doppler and biochemical markers of oxidative stress and endothelial dysfunction predict preeclampsia. STUDY DESIGN: UtA Doppler was performed at 11 to 14 and 22 to 25 weeks on 1447 asymptomatic pregnant women. Oxidative stress, endothelial dysfunction, and antiangiogenic state were assessed in women who later developed preeclampsia and normotensive controls. RESULTS: There was a significantly increased of UtA pulsatility index (PI), plasma levels of soluble fms-like tyrosine kinase 1 (sFlt1), PAI-1/PAI-2 ratio, and F-2 isoprostane in women who subsequently developed preeclampsia compared with control pregnancies. Multivariate logistic regression showed that increased UtA PI performed at 23 weeks was the best predictor for preeclampsia. CONCLUSION: This study demonstrates early changes in markers of impaired placentation, antiangiogenic state, oxidative stress, and endothelial dysfunction suggesting that these derangements may play a role in the pathogenesis of preeclampsia. Our data point to UtA as the best test to predict preeclampsia at 23 weeks of gestation.

Pathophysiological basis for the prophylaxis of preeclampsia through early supplementation with antioxidant vitamins.

Preeclampsia (PE) is a multisystem disorder that remains a major cause of maternal and foetal morbidity and death. To date, no treatment has been found that prevents the development of the disease. Endothelial dysfunction is considered to underlie its clinical manifestations, such as maternal hypertension, proteinuria, and edema; however, the precise biochemical pathways involved remain unclear. A current hypothesis invokes the occurrence of oxidative stress as pathogenically important, as suggested by the fact that in PE, the placental and circulating levels of lipid peroxidation products (F2-isoprostanes and malondialdehyde [MDA]) are increased and endothelial cells are activated. A potential mechanism for endothelial dysfunction may occur via nuclear transcription factor kappa B (NF-kappaB) activation by oxidative stress. Alternatively, the idea that the antiangiogenic placental soluble fms-like tyrosine kinase 1 factor (sFlt1) is involved in the pathogenesis of this disease is just emerging; however, other pathophysiological events seem to precede its increased production. This review is focused on evidence providing a pathophysiological basis for the beneficial effect of early antioxidant therapy in the prevention of PE, mainly supported by the biological effects of vitamins C and E.